Zebrafish genes and autistic like behavoirs

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Researchers are angling to develop better techniques to assess social behavior in zebrafish, unpublished studies presented at Neuroscience 2022 in San Diego, California, reveal. And with good reason. The fish can model aspects of autism genetics that are difficult to access in other species, other work shows.

The net impression is that despite their evolutionary distance from humans, zebrafish can say something meaningful about social behavior — and how autism-linked genes can alter it.

“I think people are getting more open to the idea in recent years,” says Yijie Geng, a postdoctoral researcher in Randall Peterson’s lab at the University of Utah in Salt Lake City.

Zebrafish are highly social, Geng and other researchers who study them say. In the wild, they are rarely alone, preferring to form loose aggregations of fish called shoals and sometimes exhibiting tighter, more coordinated schooling behavior.

One challenge is that scoring that behavior by hand is a tedious and time-consuming task, and most tests capture only a few aspects of the behavior at most. Software to analyze the fish’s behavior exists but also has limitations. “It classifies based on parameters important to us, but we don’t know if they’re important to zebrafish,” Geng says.

nter artificial intelligence. In a poster presentation on Tuesday, Geng detailed a machine-learning program called ZeChat that can analyze the behavior of up to 80 fish at a time.

Geng and Peterson deposited pairs of larval zebrafish into 2-centimeter-by-4-centimeter enclosures and separated them by a transparent piece of plexiglass that runs down the middle of each enclosure (see video above). Cameras record the fish as they interact across the barrier, and the algorithm automatically detects and classifies the behavior.

Other researchers are developing approaches using this principle, known as unsupervised deep learning, to assess the behavior of other model organism species.

“The computer isn’t a zebrafish either, but the advantage it has over a human is that it doesn’t discriminate between details,” Geng says.

The result is a map of 80 different zebrafish behaviors, some of which — such as number 8, eye movement; number 36, adjusting position during dormant phase; and number 40, switching from dormant to active at window — humans can interpret, whereas the meaning of others remains a mystery.

The algorithm describes an 80-dimensional behavioral ‘fingerprint’ for each fish based on how often it performs each of the behaviors.

Geng and Peterson used ZeChat to assess the effects of 237 different drugs on the behavior of wildtype zebrafish. Different classes of drugs produced distinct behavioral fingerprints, and compounds that have similar functions produce similar ones.

Drugs that stimulate one type of dopamine receptor increase sociability in the fish, the researchers found. The drugs make the fish more likely to stay in close proximity to the barrier, beat their tails and swim rapidly, and turn more quickly and frequently than control zebrafish.

Three different drugs in this class — pramipexole, piribedil and 7-Hydroxy-DPAT-HBr — rescue social deficits in zebrafish exposed to the anti-seizure drug valproic acid, which is linked to autism.

The research also appears in a paper posted on bioRxiv in October 2021. Geng aims to develop a version of the algorithm that could analyze the behavior of two zebrafish swimming together without being separated by a barrier.

The findings were also published in Molecular Autism in September.